Downloaded from Br. J. Nub. (1981), 45, 183 183 https://www.cambridge.org/core Factors affecting the voluntary intake of food by sheep 3. The effect of intravenous infusions of gastrin, cholecystokinin and secretin on motility of the reticdo-men and intake BY W. L. GROVUM Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, . IP address: Guelph, Ontario N1G 2W2 Canada (Received 8 November 1979 - Accepted 1 September 1980) 170.106.33.14 1. Sheep given ground and pelleted lucerne hay (Medicogo safiva) ad lib. were infused intravenously with pentagastrin, secretin, cholecystokinin (CCK) and its analogues to assess their effects on motility of the , on retido-menand on food intake. In the latter experiments the animals were deprived of their diet for periods 25 Sep 2021 at 23:31:43 of up to 6 h to induce hunger and the infusions were made before and during 3-10 min periods of feeding. 2. Pentagastrin, an analogue of gastrin, depressed intake by 3540% (P< 0.05) when it was infused at 9pglkg per h during 30 min of feeding. The threshold may however be below 1 pg/kg per h as this dose decreased intake of 12-17%. The frequency of reticular contractions decreased by 13, 35, 39 and 44% when 1, 3, 9 and 27 pg pentagastrinbg per h respectively was infused (P< 0-025). 3. Secretin depressed food intake 38% after 30min (P< 0.025) when 8 Clinical Units (CU)/kg per h was infused but the threshold could be less than this dose since 0*5CU/kg per h depressed intake by 12%. Contraction amplitude but not frequency decreased at 8 CU/kg per h. , subject to the Cambridge Core terms of use, available at 4. CCK produced a 39% decrease in intake during the fint 10 min of feeding (P< 0-05)and the threshold was between 5 and 15 Ivy Dog Units (IDU) or 425 and 1276 pmol/kg per h. The frequency of reticular contractions was not affected by 1.7 IDU/kg per h but it was depressed 21 and 63% by 5 and 15 IDU/kg per h. Octapeptide at 1.5 and 3 pg (1312 and 2624 pmol)/kg per h depressed intake by 11 and 43% respectively after 10 min (not significant) and 1.5 pg/kg per h depressed motility by 39% (P < 0.01). Ceruletide at 810 ng (599 pmol)/kg per h depressed intake by 31 % (not signi6cant) after 10 min and decreased motility by 52% (P< 0.05). The threshold dose for ceruletide on intake appeared to be about 90 ng or 66 pmol/kg per h which is considerably less than that for CCK or octapeptide. 5. The biological significance of gastrointestinal hormones as signals of satiety in normal sheep is not known since doses of pentagastrin and CCK that suppressed intake also interfered quite markedly with motility. However there is good reason to suspect that elevated concentrations of gastrin and CCK in blood of parasitized sheep may account at least in part for their symptoms of rumen atony and reduced food intakes. Interest is being shown in gastrin, secretin and cholecystokinin as signals of satiety since their concentrations in venous blood increase during a meal in human beings (gastrin: Wyllie etal. 1972;Gedde-Dahl, 1975; Fritschetal. 1976;Woussen-Colleetal. 1977;cholecystokinin: https://www.cambridge.org/core/terms Harvey et al. 1973; Johnson & McDermott, 1973; secretin: Schaffalitzky De Muckadell & Fahrenkrug, 1978) and in animals with simple stomachs (gastrin: Debas et al. 1976; Svensson et al. 1976; secretin: Kim et al. 1979). Secretin release was often observed in the more distant past in response to an infusion of acid into the duodenum but not by meals (Rhodes et al. 1976; Boden et al. 1978) partly because the assays used were not as sensitive as those of Schaffalitzky De Muckadell & Fahrenkrug (1978) and Kim et al. (1979). Injections of cholecystokinin (CCK) have depressed the intake of food by rats (Gibbs et al. 1973; Antin et al. 1975; Maddison, 1977; Antin et al. 1978; Mueller & Hsiao, 1979), mice (Strohmayer et al. 1976), monkeys (Gibbs et al. 1976), dogs (Sjiidin, 1972), rabbits . (Houpt & Anika, 1977), human beings (Sturdevant & Goetz, 1976) and sheep (Baile & https://doi.org/10.1079/BJN19810091 Grovum, 1974; Grovum, 1977a,b) but not in domestic fowl (Snapir & Glick, 1978). However CCK did not reduce intake in rats when it was injected at the start of spontaneous OOO7-1145/81/3436-0109 $01.00 0 1981 The Nutrition Society Downloaded from 184 W. L. GROVUM meals (Glick et al. 1971) and Mineka & Snowdon (1978) found that CCK injections initially depressed food intake by rats but with repeated testing on successive days the effect https://www.cambridge.org/core disappeared and there was no difference between CCK and normal saline (9g sodium chloride/l). Secretin injections were without effect on food intake in the rat (Glick et al. 1971; Gibbs et al. 1973) but secretin and pentagastrin (an analogue of gastrin with similar activity) did decrease intake by sheep (Grovum et al. 1974; Grovum, 1977a, b). The research now reported indicated that intravenous infusions of pentagastrin, secretin and CCK depressed food intake by hungry sheep. EXPERIMENTAL . IP address: Sheep and surgery Crossbred Suffolk wethers were used in all experiments. Sheep nos. 1,2,3,5 and 14 which were used.in all experiments except Expt 4(b) weighed 45 f 1 kg at the beginning of the 170.106.33.14 experiments and 62 +2 kg at the end. Sheep nos. 2,3,4,5 and 15 used in Expt 4(b) weighed 45 + 1.7 kg. The animals were treated for internal parasites with subcutaneous injections of a broad-spectrum anthelmintic (Tramisol; Cyanamid). External parasites when evident , on were killed with a dusting powder containing Malathion. The animals were fitted with rumen 25 Sep 2021 at 23:31:43 cannulas and were allowed to recover for 14d before the experiments commenced. Housing, feeding and diets The sheep were held in a room which was always illuminated. Ground and pelleted lucerne (Medicago sativa) hay (g/kg :947 dry-matter, 144(nitrogen x 6-25), 81 ash, 400 acid-detergent fibre, 27 fat) was available ad lib. except during the experimental sessions in Expt 1 and , subject to the Cambridge Core terms of use, available at during the periods of deprivation immediately before the experimental sessions in Expts nos. 2, 3, 4 and 5. Water was available continuously. Measurement of motility of the reticulum A polyethylene tube (up to 600 mm in length, 6 mm i.d., 9 mm 0.d.) with a toy balloon secured on one end and a rubber stopper on the other was directed through a rumen cannula into the reticulum and held in place by pushing the stopper into the cannula. A vinyl tube (1 m in length, 8 mm i.d., 1 1mm 0.d.) was fitted securely over the tubing protruding from the sheep and connected to a glass ‘T’ piece having a three-way stopcock attached to its side arm. Another vinyl tube (4 m in length, 5 mm i.d., 7 mm 0.d.) connecting the remaining outlet of the ‘T’ piece and a strain gauge transducer was filled with water to 100mm below the ‘T’ piece which was fixed securely to the side of the metabolism cage. The transducer was mounted on a trolley and pressures in the reticulum were recorded after 5 ml air was introduced into the balloon through the stopcock. The volume of air did not by itselfproduce https://www.cambridge.org/core/terms pressure inside the balloon. Artifact due to movement of the animal was minimal with this set up and biphasic and triphasic pressure waves during mixing and rumination cycles of motility confirmed that the balloon was in the reticulum. The portion of the polyethylene tube inside the balloon had to be perforated with holes because without these, the tip of the tube was frequently covered by the balloon and pressure changes could not be recorded. General protocol During Expt 1 food was withdrawn while hormones were infused. In Expts nos. 2,3,4 and 5 the schedule of feeding was as follows except that when ceruletide was used, intakes were . not measured after the infusion was stopped. Fresh food and water were made available https://doi.org/10.1079/BJN19810091 between 08.00 and 09.00 hours. The sheep were deprived of food but not water from 09.00 to 13.56 hours (deprivation period was 296min in this instance). Treatments were imposed (cholecystokinin was infused intravenously for example) before feeding, 13.31-1 3.56 hours and during feeding, 13.5614.30 hours. Food intakes were recorded at 0-lOmin, 13.5614.06 Downloaded from Gastrointestinal hormones and satiety 185 hours; 10-20min, 14.08-14.18 hours and 20-30min, 14.2s14.30 hours. Infusions were stopped at 14.30 hours. Food intakes were measured at 3040min, 14.33-14.43 hours. https://www.cambridge.org/core The treatments were imposed according to a 5 x 5 Latin-Square design in all experiments except Expt no. 1 but the deprivation period varied from 160 to 395min. Expt 1. Motility of the reticulum The effect of intravenous infusions of gastrointestinal hormones on motility of the reticulum was used as a biological assay to assess their physiological significance as signals of satiety. A more direct method would have been to measure concentrations of the hormones by radioimmunoassay in serum from normal sheep and those infused yith hormone but these . IP address: assays were not available for use in sheep.